1. Field of the Invention
This invention relates to etoposide soft capsules comprising soft (elastic) gelatin shells of pH 3.7 to 5.7 and, enclosed therein, an etoposide solution containing an organic acid.
2. Description of the Prior Art
Etoposide, i.e. 4'-demethylepipodophillotoxin-9-(4,6-O-ethylidene-.beta.-D-glucopyranoside ), is a drug effective for treating lung cancer, malignant lymphoma, and testicular tumor.
The etoposide capsule is an already known form of etoposide administration (cancer, April 1975, Vol. 35, No. 4, 1142). In said literature, the internal composition of the capsule is reported to contain 100 mg of etopoisde, 320 mg of Miglyol 812, 70 mg of bee'swax, and 10 mg of soya lecithin, but no mention is made of the capsule shell. In prepairing general capsules, it is a common practice to adjust pH of the shell to an approximate neutrality (pH 7) in view of the stability of the drug. The term "pH of the shell" means pH of an aqueous solution just before forming the shell.
The present inventors carried out a study on encapsulated etoposide preparations. During the study it was found that when a solution of etoposide in polyethylene glycol, for example, is enclosed in common soft gelatin shells of a pH in an approximately neutral range and the resulting capsules are stored, the enclosed etopside manifests instability with the laps of time, resulting in isomerization to picro form.